Intrinsic resistance: how bacteria are out-evolving us!
Intrinsic resistance
Without delving too deeply into the definition of the term “intrinsic resistance,” let’s explore the vast world of microorganisms that surround us, particularly bacteria and their natural ability to withstand antibiotics.
It’s well-known that many bacteria gradually become less susceptible to antibiotics due to our mishandling of these drugs. However, intrinsic resistance tells a different tale. Essentially, it refers to bacteria being inherently resistant to toxic components due to the passage of time and the process of evolution. It’s as simple as that.
Hence, it’s evident to say that antibiotic resistance is not solely a man-made problem. Instead, our misuse of antibiotics exacerbates an existing issue. The emergence of new defensive mechanisms in order to survive is a natural process — our often reckless use of antibiotics merely accelerates this process… significantly!
Intrinsich resistance — or the way evolution works
To comprehend how bacteria gradually out-evolve us, we need to understand the origins of most antibiotics used today. While medications aiding in the treatment of infectious diseases may seem like products of scientific laboratories, the majority of significant antibiotics are actually derived from molecules produced by soil microorganisms (1). Just consider the history of antibiotics: Alexander Fleming’s accidental discovery in 1928 that Penicillium releases ‘bacterial growth inhibiting substances’ in its environment. Although nowadays most antibiotics are produced in large bioreactors, it’s crucial to remember their humble origins!
Here’s a fun fact: antibiotic substances not only inhibit the growth of certain bacteria but also act as signaling molecules between some microorganisms (2).
To unravel the puzzle of how antibiotic resistances emerge in natural habitats, we must delve into evolutionary theory. And it’s impossible to discuss evolution without mentioning Charles Darwin, who laid the groundwork for principles such as ‘co-evolution,’ ’natural selection,’ and ’survival of the fittest.’ In essence, it’s about survival by adaptation to the environment. In our case, within a natural habitat (e.g., soil) filled with antimicrobial substances, this means adapting to the toxic compounds released by other microorganisms, including antibiotic producers who likely don’t aim to inhibit their own growth.
However, producers don’t release antibiotics into their environment for nothing; they’re competing for nutrients and space. Consequently, only bacteria that learn to handle these antimicrobials can continue competing with antibiotic producers. This back-and-forth struggle is so common in evolution that it even has a theory named after it: the ‘Red Queen Theory,’ inspired by the character from Alice in Wonderland. Yes, that Alice — from Wonderland. Who says biologists aren’t creative? Biologist Leigh van Valen used the quote ‘Now, here, you see, it takes all the running you can do, to keep in the same place’ to hypothesize that all animals, plants, and microorganisms are subject to constant evolutionary pressure. They must evolve to compete with their neighbors and maintain their ecological niche.
Long story short — life is cruel.
Examples of intrinsic resistance
So far, we’ve learned a lot about intrinsic resistance. Now, let’s delve into some real-life examples.
Imagine a basement, ideally your own basement, so you can emotionally connect with it. This basement represents the bacterial cell. Now, envision your basement being threatened by flooding, akin to an antibiotic making its way into the cell.
What would you do to prevent the water from damaging your basement?
You’d probably try to get your hands on some sandbags to keep the water out, much like bacteria attempt to make their cell wall impermeable to the antibiotic. It’s a simple idea, but very effective!
But let’s say all the sandbags were unavailable (thanks, neighbors!) or you couldn’t react quickly enough. What other options do we have? Well, we could focus on protecting the most important items in our basement from being submerged. Bacteria do exactly the same by hiding potential targets of the antibiotics, rendering them ineffective.
Some of you might think of using a water pump (or a bucket, for those seeking a low-budget solution) to remove the water. And once again — you’ve guessed it — we can find a similar mechanism of action in bacterial cells. Through the use of efflux pumps, they can expel harmful substances.
Apart from the tragic loss, you may have just learned the basics of intrinsic antibiotic resistance. Nature devised numerous defensive strategies long before we even considered using antibiotics to treat infectious diseases. However, this doesn’t absolve us of guilt. Remember, we’re significantly accelerating this natural process!
Nature > Humans
The assumption that antibiotic resistance is solely a man-made problem is flawed (eventhough we massively contribute to it!). Perhaps we held onto this theory for so long because we tend to believe we’re the center of the universe. In reality, nature manages most processes all by itself. We may contribute to it or try to compete with it, but we’ll never truly control nature. We must grasp this sooner rather than later to fully comprehend antibiotic resistance and preserve the effectiveness of our medications for as long as possible. One thing is clear: our planet and its microbial community don’t really prioritize us. They were here before us, and they’ll likely be here when we’re gone. Nature surpasses humans — even in the so-called Anthropocene era.
References
(1) Nesme J, Simonet P. The soil resistome: a critical review on antibiotic resistance origins, ecology and dissemination potential in telluric bacteria. Environ Microbiol. 2015 Apr;17(4):913–30. doi: 10.1111/1462–2920.12631 . Epub 2014 Dec 17. PMID: 25286745 .
(2) Fajardo A, Martínez-Martín N, Mercadillo M, Galán JC, Ghysels B, Matthijs S, Cornelis P, Wiehlmann L, Tümmler B, Baquero F, Martínez JL. The neglected intrinsic resistome of bacterial pathogens. PLoS One. 2008 Feb 20;3(2):e1619. doi: 10.1371/journal.pone.0001619. PMID: 18286176; PMCID: PMC2238818.
